S292: SUSTAINED RESPONSE OFF TREATMENT IN ELTROMBOPAG-TREATED PATIENTS WITH ITP WHO ARE REFRACTORY OR RELAPSED AFTER FIRST-LINE STEROIDS: PRIMARY ANALYSIS OF THE PHASE II TAPER TRIAL
Authors: N. Cooper, W. Ghanima, N. Vianelli, D. Valcárcel, I. Yavaşoğlu, A. Melikyan, E. Yañez Ruiz, J. Haenig, J. Lee, J. Maier, N. Zolkin, F. Zaja
Journal: HemaSphere (2022)

Background: Corticosteroids (CSs) are the standard 1st-line treatment for primary immune thrombocytopenia (ITP); however, long-term CS use is associated with high relapse rates and considerable toxicity. Treatments that achieve a sustained response and reduce the need for long-term CS use are needed. Eltrombopag (EPAG) is a thrombopoietin receptor agonist (TPO-RA) indicated in Europe for the treatment of patients (pts) aged ≥1 year with primary ITP lasting ≥6 months who are refractory to other treatments (eg, CSs). Evidence suggests that a proportion of pts treated with TPO-RAs achieve sustained responses that are maintained after TPO-RA tapering and discontinuation; however, much of the evidence is retrospective with only a few prospective studies investigating sustained response off treatment (SRoT). Aims: TAPER (NCT03524612), a Phase II, open-label, prospective, single-arm study, aims to determine whether EPAG can induce SRoT in pts with ITP after 1st-line CS failure. Methods: Adult (≥18 years) pts with ITP who did not respond to or had relapsed after initial CS therapy, with platelet counts <30×109/L and assessed as needing treatment, were included. Patients received a 50 mg/day starting dose of EPAG (25 mg/day for East/Southeast Asian pts; 12.5 mg/day for Japanese pts in Japan), which could be increased up to 75 mg/day (50 mg/day in Japan) if needed. The primary endpoint was the number (%) of pts with SRoT by Month 12; SRoT was defined as achieving a complete response (CR, ie, platelet count ≥100×109/L), then maintaining a stable platelet count (no counts <70×109/L) for 2 months, followed by successful EPAG tapering and discontinuation with platelet counts ≥30×109/L and no bleeding events or rescue therapy. Patients with SRoT at Month 12 were followed for a further year. Secondary outcomes included SRoT duration and platelet count changes from baseline. Data to Month 12 are presented. Results: N=105 pts were enrolled. The median (interquartile range [IQR]) age was 46 (30-65) years; 61% were female. In the 1st 12 months, median (IQR) duration of exposure to EPAG was 5.6 (2.3-11.9) months and median (IQR) EPAG dose was 57.1 (37.5-69.0) mg/day. Overall, 89 pts (85%) achieved CR at least once and 65 pts (62%) maintained a platelet count ≥70×109/L for 2 months after CR. EPAG tapering and discontinuation was achieved in 44 pts (42%). The primary endpoint was met, with 32 pts (30.5% [95% confidence interval, 21.9-40.2]; P<0.001 [H1: P>15%; alpha: 0.05]) achieving SRoT until Month 12 (Fig. 1); SRoT was maintained from last dose to Month 12 for a median (IQR) of 33.3 (25.7-45.3) weeks. The median (IQR) absolute increase in platelet counts from baseline at Month 12 was 77.0×109/L (35.0-145.0). All-grade adverse events (AEs) occurred in 92/105 (88%) pts (grade ≥3 AEs: 33/105 [31%]). Treatment-related AEs occurred in 37 (35%) pts (8 [7.6%] grade ≥3). The most common all-grade AEs were headache (21% of pts with ≥1 event [grade ≥3: 1% of all pts]), thrombocytopenia (17% [10.5%]), and petechiae (11% [1%]). There were 4 deaths (none were considered treatment related): 3 were on-treatment (central nervous system hemorrhage [n=1], intracranial hemorrhage [n=1], metastases to peritoneum [n=1]) and 1 death (malignant neoplasm) occurred 238 days after last dose. Image:Summary/Conclusion: Data from the TAPER study indicate that a significant proportion of pts experience sustained response following tapering and discontinuation of EPAG, even after a relatively short duration of exposure. Overall EPAG was well tolerated with no unexpected AEs.